DESCRIPTION: The purpose of this proposal is to generate appropriate reagents for specific targeting and expression of therapeutic genes for treatment of colon cancers. For this study, the conditionally toxic herpesvirus thymidine kinase gene in combination with ganciclovir will be used as the therapeutic gene, and green fluorescent protein will be used as a reporter gene. These genes will be delivered via recombinant murine retrovirus to a unique panel of human cell lines derived from resected normal, pre-malignant and malignant colon tissues by InCell Corporation. Two innovative strategies to increase tumor-specific targeting and expression of therapeutic vectors will be evaluated. One strategy involves incorporation and expression of selections into the retroviral packaging cell lines to target tumor specific carbohydrate antigens. The other strategy will be to test a Tcf-4/beta-catenin responsive promoter for tumor-specific expression of the therapeutic gene. Promising therapeutic strategies will then be tested in tissues derived from a rat colon carcinogenesis model, primary human colon tumor tissues, and a human colon tumor modeling system. Commercially, both the selectin targeting and Tcf-transcription approaches will be developed for clinical gene delivery strategies for colon and other epithelial adenocarcinomas. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE